RT Journal Article
SR Electronic
T1 Lack of TRPM5-Expressing Microvillous Cells in Mouse Main Olfactory Epithelium Leads to Impaired Odor-Evoked Responses and Olfactory-Guided Behavior in a Challenging Chemical Environment
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0135-17.2017
DO 10.1523/ENEURO.0135-17.2017
A1 Lemons, Kayla
A1 Fu, Ziying
A1 Aoude, Imad
A1 Ogura, Tatsuya
A1 Sun, Julianna
A1 Chang, Justin
A1 Mbonu, Kenechukwu
A1 Matsumoto, Ichiro
A1 Arakawa, Hiroyuki
A1 Lin, Weihong
YR 2017
UL http://www.eneuro.org/content/early/2017/06/05/ENEURO.0135-17.2017.abstract
AB The mammalian main olfactory epithelium (MOE) modifies its activities in response to changes in the chemical environment. This process is essential for maintaining the functions of the olfactory system and the upper airway. However, mechanisms involved in this functional maintenance, especially those occurring via paracrine regulatory pathways within the multicellular MOE, are poorly understood. Previously, a population of non-neuronal, transient receptor potential M5-expressing microvillous cells (TRPM5-MCs) was identified in the MOE and the initial characterization of these cells showed that they are cholinergic and responsive to various xenobiotics including odorants at high concentrations. Here, we investigated the role of TRPM5-MCs in maintaining olfactory function using transcription factor Skn-1a knockout (Skn-1a-/-) mice, which lack TRPM5-MCs in the MOE. Under our standard housing conditions Skn-1a-/- mice do not differ significantly from control mice in odor-evoked electro-olfactogram (EOG) responses and olfactory-guided behaviors including finding buried food and preference reactions to socially and sexually relevant odors. However, following a two-week exposure to high concentration odor chemicals and chitin powder, Skn-1a-/- mice exhibited a significant reduction in their odor and pheromone-evoked EOG responses. Consequently, their olfactory-guided behaviors were impaired compared to vehicle-exposed Skn-1a-/- mice. Conversely, the chemical exposure did not induce significant changes in the EOG responses and olfactory behaviors of control mice. Therefore, our physiological and behavioral results indicate that TRPM5-MCs play a protective role in maintaining the olfactory function of the MOE.Significance Statement The main olfactory epithelium (MOE) detects odor molecules and provides sensory inputs for behavioral guidance and modification of the psychological state. Additionally, the MOE protects the brain and respiratory organs by providing an epithelial barrier and biotransforming xenobiotics. The MOE directly faces the respiratory airstream and is vulnerable to damage caused by inhaled odorous irritants, pollutants and infectious agents. Little is known about the mechanisms that detect xenobiotics and modulate MOE activity for functional maintenance. This study shows that transient receptor potential M5-expressing microvillous cells (TRPM5-MCs) play an important role in maintaining MOE physiologic responses to odorants and pheromones in a challenging chemical environment, and subsequently olfactory-guided behaviors. Therefore, these results revealed a novel TPM5-MC-mediated intercellular regulatory pathway.